Recent studies of human cognitive function suggest that memory systems in the brain are mediated by anatomically separate (but interactive) neural systems. An important distinction is betweene explicit and implicit memory. Implicit learning and memory refer to the acquisition and expression of information not accompanied by awareness of its content or influence on behavior. Within implicit memory/learning there are probably several subsystems. A notable type of implicit memory is "skill" or "procedural" learning, where performance improves on behavioral or cognitive skills over repeated trials, e.g. assessed using improved speed on performance of a maze task or on the serial reaction time task (SRT). Data strongly suggest that the basal ganglia play a prominent role in sequence learning. The current experiments are to explore the hypothesis that performance of implicit learning paradigms will be impaired in subjects with Huntington's disease (HD), a dominantly inherited subcortical/basal ganglia disorder, compared to matched healthy control subjects. We predict that the above implicit learning performance impairments will be associated with aberrant patterns of cerebral activation on functional MRI (fMRI) and in HD, magnitude of implicit learning performance deficit is correlated with severity of the fMRI activation abnormality. We have now imported the SRT task into the fMRI environment, shown robust basal ganglia activation in normal volunteers and demonstrated preliminarily, deficient basal ganglia activation in early HD subjects.